Entacapone and Tolcapone, Two Catechol O-Methyltransferase Inhibitors, Block Fibril Formation of -Synuclein and -Amyloid and Protect against Amyloid-induced Toxicity*

Entacapone and Tolcapone, Two Catechol-o-methyltransferase Inhibitors (icomt), Block Fibril Formation of Α-synuclein and Β-amyloid and Protect against Amyloid Induced Toxicity

Running title: Entacapone and Tolcapone inhibit Syn fibrillization * To whom correspondence should be addressed: Prof. Hilal A. Lashuel; Fax: +41 1 693 17 80; Email: [email protected]. Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease (AD). There is considerable consensus that the increased production and/or aggregation of α-synuclein (α...

Synergistic inhibition of lung cancer cell lines by (-)-epigallocatechin-3-gallate in combination with clinically used nitrocatechol inhibitors of catechol-O-methyltransferase.

(-)-Epigallocatechin-3-gallate (EGCG) has exhibited been studied for lung cancer inhibitory activity in vitro and in animal models, but it is rapidly methylated and inactivated by catechol-O-methyltransferase (COMT). Entacapone and tolcapone, COMT inhibitors, are used to mitigate the symptoms of Parkinson's disease. We investigated the synergistic effects of entacapone/tolcapone and EGCG agains...

Comparison of the hepatic safety of catechol-O-methyltransferase inhibitors entacapone and tolcapone with special reference to uncoupling of oxidative phosphorylation

Elucidating Differences in the Hepatotoxic Potential of Tolcapone and Entacapone With DILIsym®, a Mechanistic Model of Drug‐Induced Liver Injury

Tolcapone and entacapone are catechol-O-methyltransferase (COMT) inhibitors developed as adjunct therapies for treating Parkinson's disease. While both drugs have been shown to cause mitochondrial dysfunction and inhibition of the bile salt export protein (BSEP), liver injury has only been associated with the use of tolcapone. Here we used a multiscale, mechanistic model (DILIsym(®)) to simulat...

Utility of tolcapone in fluctuating Parkinson’s disease

Fluctuating Parkinson's disease (PD) represents a clinical management challenge. The primary utility of levodopa in patients with PD is moderated by the "wearing off" phenomena seen with long-term use. COMT inhibitors slow down the rapid metabolism of levodopa, resulting in a more-sustained response to dopaminergic therapy. Tolcapone is a selective, reversible catechol-O-methyltransferase (COMT...